E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7 |
E.1.2 | Level | low |
E.1.2 | Classification code | 10012613 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the response to treatment in patients with type 2 diabetes mellitus treated with RO4389620 when administered at increasing doses up to 200 mg BID. Response to treatment is defined by the percentage of patients with FPG <100 mg/dl without episodes of severe hypoglycemia |
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E.2.2 | Secondary objectives of the trial |
• To assess efficacy of RO4389620 administered at increasing doses up to 200 mg BID • To evaluate the safety and tolerability of RO4389620 when administered at increasing doses up to 200 mg BID • To evaluate in an exploratory manner possible trends in demographic and biologic parameters and safety and tolerability in patients requiring doses of RO4389620 up to 200 mg BID
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Inclusion Criteria at Screening:
1. Age 18 to 75 years at the time of the screening examination 2. Willingness and ability to give written informed consent and to comply with the requirements of the study. Legally effective written informed consent must be obtained prior to completing any study procedures or discontinuing any medications in order to qualify for study enrollment. • Patients who cannot follow self monitoring of blood glucose and study requirements independently from another person cannot be included. 3. Type 2 diabetes mellitus treated with one oral antihyperglycemic agent, administered according to labeling for at least 3 months prior to screening 4. HbA1c ≥ 7.0 % and ≤ 10.0 % at screening 5. BMI ≤ 45 kg/m2 at screening |
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E.4 | Principal exclusion criteria |
Exclusion Criteria at screening:
1. Type 1 diabetes mellitus 2. Fasting serum C-peptide < 1 ng/ml 3. Treatment with insulin during the last 3 months prior to the screening visit 4. Treatment with PPARγ agonist (e.g. Actos®, Avandia®, Avandamet®, Avandaryl®) during the last 3 months prior to screening 5. Systemic use of corticosteroids during the last 3 months prior to screening 6. Treatment with inhaled corticosteroids unless patient has been on a stable dose of ICS for 1 month prior to screening and will continue as such throughout study participation 7. Impaired liver function (ALT, AST, total and direct bilirubin or alkaline phosphatase > 2.5 x ULN) at screening 8. Serum creatinine ≥ 2.0 mg/dl (≥ 177 μmol/L) at screening 9. Blood pressure (SBP>150 mm Hg and DBP>90 mm Hg) without treatment or with stable treatment for > 3 months, labile or uncontrolled hypertension 10. Myocardial infarction or stroke within 6 months prior to the screening examination 11. Proliferative diabetic retinopathy 12. Any abnormality in clinical laboratory tests or ECG, which precludes safe involvement in the study as judged by the Investigator 13. Pregnancy or breast feeding 14. Female patients of childbearing potential who, with their partners refuse to use two forms of contraception (including 1 barrier method) from screening and for 1 month following the last study medication intake 15. Participation in an investigational drug study within 90 days (3 months) prior to screening 16. Serious illness, such as active cancer, major active infection, severe psychiatric disorders at the time of the screening examination 17. History or evidence of alcohol or drug abuse
Exclusion Criteria at Baseline:
1. Treatment with insulin and/or any antihyperglycemic agent during washout period 2. FPG <100 mg/dl at Visit 3 3. Systemic use of corticosteroids during the washout period 4. Treatment with inhaled corticosteroids during the washout period unless patient has been on a stable dose of ICS for 1 month prior to screening and will continue as such throughout study participation 5. Systemic use of strong CYP450 3A4 inducers (such as rifampicin), or potent CYP450 3A4 inhibitors (such as, but not limited to, atazanavir, clarithromycin, erythromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin or voriconazole) during washout period 6. Impaired liver function (baseline ALT, AST, total and direct bilirubin or alkaline phosphatase > 2.5 x ULN) at Visit 3 7. Serum creatinine ≥ 2.0 mg/dl (≥ 177 μmol/L) at Visit 3 8. Positive pregnancy test in women of child bearing potential 9. Blood pressure (SBP>150 and DBP>90) without treatment or with stable treatment for > 3 months, labile or uncontrolled hypertension at baseline 10. Diagnosis or evidence of any new clinically significant diseases that may preclude patient from participating in the study. Clinical significance will be assessed per investigator’s judgment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The percentage of patients at each dose who achieved FPG<100 mg/dl and did not experience episodes of severe hypoglycemia for the duration of the study |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study will be defined as the date of the last visit for the last patient. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 7 |